Papillomaviruses induce benign tumors in a variety of vertebrate species including man. These benign tumors, papillomas, can arise on a variety of squamous epithelial surfaces such as skin, larynx, and genitalia. In some cases, these benign viral-induced lesions can progess to carcinomas. Papillomas induced by the Shope pappillomarivus (in rabbits) or the bovine papillomavirus type 4 (in cattle) can develop into carcinomas, and in humans the occurrence of cervical dysplasia and its progression to cervical carcinoma is closely associated with human papillomavirus types 16 and 18. In both animals and man it is believed that the papillomaviruses interact with additional factors (e.g., carcinogens and/or tumor promoters) to effect the complete transformed phenotype. The intent of our laboratory's investigations is to define the mechanism by which papillomaviruses transform immortalized cells in vitro and to determine how they contribute to tumorigenesis in vivo. Specifically, we are studying the transforming activities of cloned papillomavirus DNA as determined by focus assays and tumorigenicity in nude mice. We are also committed to identifying and characterizing the transforming proteins encoded by these viruses. To date, we have been able to demonstrate that the bovine papillomavirus effects the synthesis of an unusually small transforming polypeptide. This small protein, which is the product of the E5 open reading frame, is hydrophobic and is localized in cellular membranes. We have also been able to demonstrate that human papillomavirus DNA can covert NIH 3T3 cells to the tumorigenic state.